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Some missions of discovery confronted ''Enterprise'' with entities and mechanisms that threatened great swaths of Federation and neighboring space.
An ancient "[[Doomsday machine]]", fueled by the consumption of planets it destroyed with its [[{{MA|Antiproton|antiproton]] [[}} weapon]], approached Federation population centers in 2267. It required the combined efforts of the ''Enterprise'' and her sister ship {{USS|Constellation|NCC-1017}} to destroy it.
A [[space amoeba|single-cell organism]] of colossal scale emitted [[negative energy]] toxic to [[humanoid]] life, killing the entire [[Vulcan]] crew of the {{USS|Intrepid|NCC-1631}}. The ''Enterprise'' penetrated the [[cell]] interior and destroyed the organism before its imminent cell division threatened to overwhelm the rest of the galaxy.
